Dissociation between post-surgical pain behaviors and spinal Fos-like immunoreactivity in the rat

Previous studies have demonstrated that Fos-like immunoreactivity is increased in spinal dorsal horn neurons in several pain models, and have suggested that Fos-like immunoreactivity could be used as a marker of neurons activated by painful stimulation. In the present study, we evaluated nociceptive behaviors and spinal Fos-like immunoreactivity in a rat skin incision model of post-operative pain. In this model, evoked and non-evoked pain behaviors were observed at least for 2 days after paw surgery, an increased number of Fos-like immunoreactive neurons was observed in the spinal dorsal horn at lumbar levels 4–5 two-hour post-surgery. The number of Fos-like immunoreactive neurons was significantly greater in animals with skin–muscle incision compared to animals with skin-alone incision. Interestingly, spinal Fos-like immunoreactivity was quickly normalized in rats with paw surgery at later time points (8 and 24 h post-surgery), whereas nociceptive behaviors were still observed. Furthermore, at 24 h post-surgery, spinal Fos-like immunoreactivity induced by thermal stimulation (42, 44, 46, 48, 52 °C for 15 s) was not significantly different between sham animals and animals with surgery. In both groups, an increase in spinal Fos-like immunoreactive neurons was observed with increasing temperatures, with similar laminar distribution. Finally, systemic morphine reduced post-operative pain and Fos-like immunoreactivity in a naloxone reversible manner, with greater potency and efficacy on behavioral endpoints than on Fos-like immunoreactivity. These results demonstrate a different profile of nociceptive behaviors and spinal Fos-like immunoreactivity in the rat skin incision model, suggesting a limited potential of spinal Fos-like immunoreactivity to study post-surgical pain and its pharmacology.